There is strong evidence that an increase in the long chain fatty acids and their acyl derivatives (acyl-CoA, acyl-carnitine and lyso-phospholipids) is occurring in brain during early onset of cerebral ischemia. An increase in the acyl-containing compounds in cerebral ischemia may be the primary factor affecting the mitochondrial respiratory control and synaptosomal membrane transport activities. The main objective of this research program is to investigate the biochemical mechanism underlying the ischemia-induced accumulation of free fatty acids and acyl-containing compounds in brain and to examine the effects of these acyl compounds on neuronal membrane functions. Specifically, (1) the activity of phospholipase A2 in cerebral cortex synaptosomes will be correlated with different times after ischemic treatment. The effects of neuroleptic drugs, local anesthetics and barbiturates on synaptosomal phospholipase A2 activity will be evaluated. (2) The level of free fatty acids, acyl-CoA, acyl-carnitine and lyso-phosphoglycerides will be determined in specific brain regions in controls and ischemic samples. (3) The activity of acyl-CoA hydrolase and fatty acid: CoASH ligase in brain will be examined with respect to ischemic treatment. (4) The effects of acyl-derivatives on synaptosomal (Na ion, K ion)-ATPase activity and Ca ion uptake will be evaluated. Since many of the above processes are known to be affected by Ca ions, the effects of calcium and calmodulin on the acyl metabolism in synaptosomes will be evaluated. Ischemia will be produced by decapitation of rats or mice, and by ligation of the right common carotid artery of the gerbils. It is anticipated that results from the investigation would lead to a better understanding of the biochemical basis underlying the altered fatty acid metabolism in cerebral ischemia. Furthermore, information regarding the effects of natural occurring fatty acyl compounds on neuronal membrane functions will be important in evaluating the effects of neuroleptics, barbiturates and psychotropic drugs on alleviating the pathophysiological symptoms due to the ischemia insult.